Biomarker promising for predicting HPV-related oropharynx cancer

Antibodies against the human papillomavirus (HPV) may help identify those with a greatly increased risk for HPV-related cancer of the oropharynx, which is a portion of the throat that contains the tonsils.

This new study found that at least one in three persons with oropharyngeal cancer had antibodies to HPV, compared to fewer than one in 100 persons without cancer. When present, these antibodies were detectable many years before the onset of disease. These findings raise the possibility that a blood test might one day be used to identify patients with this type of cancer. The study's results were published in the Journal of Clinical Oncology (2013; doi:10.1200/JCO.2012.47.2738).

Historically, the majority of oropharyngeal cancers could be explained by tobacco use and alcohol consumption rather than HPV infection. However, incidence of this malignancy is increasing in many parts of the world, especially in the United States and Europe, because of increased infection with HPV type 16 (HPV16). In the United States, an estimated more than 60% of current cases of oropharyngeal cancer are due to HPV16. Persistent infection with HPV16 induces cellular changes that lead to cancer.

HPV E6 is one of the viral genes that contribute to tumor formation. Previous studies of patients with HPV-related cancer of the oropharynx discovered antibodies to E6 in the patients' blood.

“Our study shows not only that the E6 antibodies are present prior to diagnosis—but that in many cases, the antibodies are there more than a decade before the cancer was clinically detectable, an important feature of a successful screening biomarker,” said lead investigator Aimee R. Kreimer, PhD, of the National Cancer Institute in Washington, DC.

Kreimer and her colleagues tested samples from participants in the European Prospective Investigation into Cancer and Nutrition Study, a long-term study of more than 500,000 healthy adults in 10 European countries. Participants gave a blood sample at the start of the study and have been followed since their initial contribution.

The researchers analyzed blood from 135 persons who developed oropharyngeal cancer between 1 and 13 years later, and nearly 1,600 control persons who did not develop cancer. The study found antibodies against the HPV16 E6 protein in 35% of the persons with cancer, compared to less than 1% of the samples from the cancer-free persons. The blood samples had been collected on average, 6 years before diagnosis, but the relationship was independent of the time between blood collection and diagnosis. Antibodies to HPV16 E6 protein were even found in blood samples collected more than 10 years before diagnosis.

The scientists also report that HPV16 E6 antibodies may be a biomarker for improved survival, consistent with previous reports. Patients in the study with oropharyngeal cancer who tested positive for HPV16 E6 antibodies prior to diagnosis were 70% more likely to be alive at the end of follow-up, compared to patients who tested negative.